To clarify the mechanisms leading to fibrosis in and the immunologic abnormalities associated with human silicosis a model of experimental silicosis in guinea pigs will be developed and examined employing in vitro immunologic and tissue culture techniques. The guinea pig has been chosen since pulmonary silicotic nodules can be provoked by inhalation or injection of silica particles and the normal immunologic function of this species has been extensively studied in our laboratory. The proposed studies have been divided into three major areas: 1. Effect of intratracheal injection of silica on quantitative and qualitative properties of immunocompetent cells in the lung and systemic immune system (blood, lymhoid tissue). 2. Macrophage monocyte kinetics in acutely and chronically silica exposed host. 3. Factor(s) which may be important in promoting fibrosis in silicotic lesions. Properties of lymphocytes isolated from the blood, tracheobronchial lymph node and lung to be examined include relative proportions of T and B cells, proliferative response to mitogens and antigens (PPD), and lymphokine production. Properties of lung and peritoneal macrophages to be studied include response to chemotactic stimuli, phagocytic capacity, membrane activation, and accessory cell function in lymphocyte stimulation. By in vivo labeling of recently divided phagocytic mononuclear cells the effect of chronic silica exposure on macrophage recruitment into the lung will be assessed. Factors recruiting these cells will be tested for in an in vitro chemotactic assay. Finally fibroblast cultures will be used to detect factors derived from silica treated immunocompetent cells which promote accumulation of collagen.